The long-term objective of this project is to understand the mechanisms of K + channel gating, that is, how the opening of K + channels is regulated in living cells. Potassium channels play a central role in many different cellular processes including the production of electrical impulses in the nervous system, the control of heart rate, blood pressure, and the secretion of hormones such as insulin. For these reasons, a deeper understanding of how K+ channels open and close - based on their chemistry and structure -will eventually enhance our ability to treat many illnesses that afflict humans, including seizure disorders, cardiac arrhythmias, hypertension, and asthma. A wide range of techniques will be applied to the study of K + channel gating, including molecular biology, protein biochemistry, electrophysiology, and X-ray crystallography. Three fundamentally different gating mechanisms will be studied: channel opening induced by Ca 2+ binding, by G-protein binding, and by membrane voltage. The first of these mechanisms underlies muscle contraction and signal processing in the nervous system, the second mechanism controls heart rate and neurotransmitter responses, and the third is responsible for generating electrical impulses known as action potentials in both nervous and non-nervous cells.